Autologous Dendritic Cell Therapy for Type 1 Diabetes Suppression: A Safety Study

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by University of Pittsburgh.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00445913
First received: March 7, 2007
Last updated: February 18, 2011
Last verified: February 2011
  Purpose

The proposed studies describe a randomized trial to evaluate the safety of a new diabetes-suppressive cell vaccine, consisting of autologous monocyte-derived dendritic cells treated ex vivo with antisense phosphorothioate-modified oligonucleotides targeting the primary transcripts of the CD40, CD80 and CD86 co-stimulatory molecules (immunoregulatory DC; iDC). The hypothesis to be tested in this study is that iDC are safe and without toxicity in established type 1 diabetic patients.

Fifteen (15) individuals exhibiting fully-established, insulin-dependent type 1 diabetics, without any diabetes-related complications, infectious disease, or other medical anomaly, will be enrolled to establish safety of the approach. 7/15 volunteers will be administered autologous control dendritic cells and 8/15 will be administered iDC. The study is anticipated to be complete by twelve (12) months.

Currently, other than a humanized anti-CD3 antibody with considerable side effects, there is no other means to reverse new-onset type 1 diabetes. These studies will be the first ever to employ autologous dendritic cell transfer to suppress an autoimmune disease and to perhaps reverse it early on in the clinical process.


Condition Intervention Phase
Diabetes Mellitus, Insulin-Dependent
Biological: Diabetes-suppressive dendritic cell vaccine
Biological: control dendritic cells
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Autologous Dendritic Cell Therapy for Type 1 Diabetes Suppression: A Safety Study

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • The trial is designed to assure that the toxicity rate is acceptably low to warrant further study of the cell vaccine in efficacy trials. [ Time Frame: June 2011 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: March 2007
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: control dendritic cells
autologous dendritic cells that are not treated
Biological: control dendritic cells
The dendritic cells will be treated ex vivo with vehicle and cryopreserved in aliquots for subsequent intradermal administration into sites closest to the physical location of the pancreas inside the body. Physiologic, biologic and immunologic responses to these control dendritic cells will be evaluated over the period of the trial. The first group of volunteers will receive autologous dendritic cells without any ex vivo treatment (7/15) and the second group will be administered iDC (8/15). If there is no evidence of toxicity or adverse events associated with the dendritic cell vaccine, and only upon FDA and IRB approval we will initiate a new study comparing efficacy of control DC and iDC in improving glycemia and reversing autoimmunity in new-onset patients.
Other Name: control dendritic cells
Experimental: AS ODN dendrtitic cells
autologous dendritic cells treated ex vivo with the mixture of the antisense oligonucleotides
Biological: Diabetes-suppressive dendritic cell vaccine
The dendritic cells will be treated ex vivo with the antisense oligonucleotides and cryopreserved in aliquots for subsequent intradermal administration into sites closest to the physical location of the pancreas inside the body. Physiologic, biologic and immunologic responses to the dendritic cell vaccine will be evaluated over the period of the trial. The first group of volunteers will receive autologous dendritic cells without any ex vivo treatment (7/15) and the second group will be administered iDC (8/15). If there is no evidence of toxicity or adverse events associated with the dendritic cell vaccine, and only upon FDA and IRB approval we will initiate a new study comparing efficacy of control DC and iDC in improving glycemia and reversing autoimmunity in new-onset patients.
Other Name: diabetes-suppressive dendritic cells

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Patients with established type 1 diabetes mellitus who meet all inclusion criteria are eligible for enrollment in the study.

  • All patients enrolled must be on insulin replacement therapy.
  • Written informed consent conforming to the institutional guidelines obtained from the patient.
  • Documented evidence of insulin-requiring type 1 diabetes of >5 years duration.
  • Adequate immune competence, as indicated by positive reaction to one or more of the common DTH skin tests that are part of the Multitest CMITM test system (Pasteur-Merieux Connaught) and as indicated by the manufacturer. Also, proof of vaccination for tetanus (no more than 10 years must have elapsed between tetanus vaccination and the onset of this study).
  • Age 18-35.
  • Adequate hematologic function:

    • Absolute neutrophil count > 1,000/mm3
    • Absolute lymphocyte count > 1,000/mm3
  • Hemoglobin > 9 gm/dl
  • Platelets > 100,000/mm3
  • Liver function tests:

    • Bilirubin (total) < 1.7 mg/dl
    • Alkaline phosphatase < 78 u/L (2 x ULN)
    • SGOT < 54 u/L (2 x ULN)
    • Lactic dehydrogenase < 180 u/L (2 x ULN)
  • Kidney profile:

    • Serum electrolytes

      • Sodium 135-145 mEq/L
      • Potassium 3.5-5.0 mEq/L
      • Bicarbonate 21-28 mEq/L
      • Chloride 100-108 mmol/L
      • Serum creatinine <4.5 mg/dL (3 x ULN)
      • BUN 8-25 mg/dL
      • No prior history of radiation therapy, immunotherapy, or chemotherapy
      • Evidence of prior immunization to tetanus
      • Absence of HIV, HSV, HBV, HCV viral infections
      • At least four weeks since any prior radiation , immunotherapy or chemotherapy

Exclusion Criteria:

  • One or more of the Eligibility Criteria are not met.
  • A significant history or current evidence of cardiac disease including, but not limited to, congestive heart failure, coronary artery disease, angina pectoris, uncontrolled hypertension, serious arrhythmias; or myocardial infarction within the previous six months.
  • Evidence of active infection requiring antibiotic therapy.
  • History of other concurrent diseases.
  • Pregnant or lactating women.
  • Patients requiring systemic corticosteroids
  • Any other immune disorder including but not limited to other autoimmune diseases like rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, or ankylosing spondylitis
  • Pregnancy
  • History of radiation therapy, immunotherapy, or chemotherapy
  • Breastfeeding
  • The following therapies cannot be administered while patients are undergoing treatment on this protocol:

    • radiation therapy
    • chemotherapy
    • corticosteroids (except when administered in life-threatening circumstances) other particle or cell vaccine therapies

At the time of screening, the patients will be tested for evidence of the following viral infections: HIV, HBV, HCV, herpes, CMV and EBV. In addition, female volunteers will be asked to provide documentation from their physician stating that they have not tested positive for the HPV viral infection. Only patients testing negative for ALL these viral infections will be further considered. Should any volunteer be excluded on grounds of positivity for any of these infectious agents, they will be immediately notified and strongly advised to consult their physician. The data and the records will be maintained under lock and in the study participation file of the volunteer until the volunteer confirms in writing that they have notified their physician. At that time, these specific data may be submitted to the patient's physician ONLY DIRECTLY BY THE VOLUNTEER upon written request to the study principal investigator or immediately destroyed.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445913

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Massimo Trucco, M.D. University of Pittsburgh
  More Information

Publications:
Responsible Party: Massimo Trucco, M.D., Rangos Research center
ClinicalTrials.gov Identifier: NCT00445913     History of Changes
Other Study ID Numbers: 0509115, NIDDK R33 DK683044
Study First Received: March 7, 2007
Last Updated: February 18, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
type 1 diabetes
dendritic cells
cell vaccine
safety
reversal

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 22, 2014